After 30 Years, Why Don't We Have An HIV Vaccine?

Three studies published Thursday make modest advances toward finally developing a vaccine against HIV. Despite billions of dollars in funding, researchers say they’re still far from solving one of the hardest scientific problems of our time.

On April 23, 1984, three years into the discovery of a mysterious disease that had killed more than 1,000 mostly gay men, then-Secretary of the U.S. Department of Health and Human Services Margaret Heckler called a press conference.

Over the course of the highly publicized event, Heckler told the crowd three pieces of good news: Scientists had discovered the virus behind AIDS, a test was available to identify it inside of infected people, and a vaccine against the disease was just two years away.

Even at the time, scientists knew that Heckler's claims were too optimistic. Her remarks seem hopelessly naive today, some three decades on, as scientists still struggle to develop a successful vaccine.

AIDS has claimed nearly 39 million lives to date, and HIV infects more than 2 million people each year. For people with access to antiretroviral drugs, the virus is no longer the death sentence it used to be. But to actually end the global epidemic, experts say, we need a vaccine.

On Thursday, threescientificpapers came out in top-tier journals describing new molecular insights into coaxing the immune system to attack HIV. Researchers are thrilled by these results, which promise to significantly advance the vaccine effort. But the field's veterans also know, by now, not to put too much stock in early stages of research.

"It's been a very big priority, but it's also been a research area that's been plagued with setbacks and disappointments," Mark Harrington, executive director of the Treatment Action Group, an AIDS research and policy think tank, told BuzzFeed News.

The problem boils down to the fact that HIV is an incredibly diverse virus, and also mutates rapidly within our bodies.

"Everyone's effectively infected with a unique strain," William Schief, professor of immunology at the Scripps Research Institute and co-author of all three new papers, told BuzzFeed News. "There's really 30 million different viruses."

In normal vaccines, such as those for measles or smallpox, a weakened or dead virus induces our cells to produce proteins, called antibodies, to attack that specific virus. Once our immune cells learn which antibodies to produce against a specific virus, we are essentially protected for life.

To create a successful vaccine against HIV, however, the body needs to produce a defense arsenal capable of fighting a constantly mutating target. Antibodies, which normally have very specific targets, would need to be able to recognize and attack a wide range of enemies.

The first hint of how that might be possible came in 2010, when government scientists discovered three antibodies more powerful than any others previously identified in humans. Found in the cells of a 60-year old black gay man known as Donor 45, these so-called broadly neutralizing antibodies, or BNABs, had the ability to neutralize up to 91% of HIV strains.

Since then, researchers have discovered dozens more BNABs in a small number of HIV-infected patients whose bodies are — for unknown reasons — able to produce them on their own after two to three years of harboring the virus.

For those HIV-positive individuals, unfortunately, the antibodies are too little too late. Figuring out a way to make uninfected people produce them to stave off HIV before it can take hold of their immune systems is the "holy grail" of current vaccine research, Bruce Walker, director of a multi-institution HIV vaccine effort called the Ragon Institute, told BuzzFeed News.

The discovery of these antibodies has led to a "renaissance" in HIV vaccine research, Wayne Koff, chief scientific officer of the International Aids Vaccine Initiative, told BuzzFeed News. "It's probably the most exciting time that's ever existed for HIV vaccine research."

However, no one has yet been able to induce these antibodies outside of the handful of individuals who can produce them on their own.

The three new scientific papers suggest that it might be possible to reverse-engineer the way immune cells make BNABs.

One team of researchers constructed a very close mimic of the three-pronged structure on HIV that allows the virus to latch on to human cells. Because this structure is a crucial part of how the virus attacks — and because this component has some of the few patches of DNA that do not change across the many million different strains of HIV — it's a good target for an antibody.

"HIV is a crafty virus — we've learned that the hard way over the years," Koff said. "But this is its achilles heel."

With this model of the structure now in hand, the researchers hope to figure out a way to induce an antibody called VRC01, one of the BNABs originally found in Donor 45, that binds to it and prevents it from infecting human cells.

"If we can't do that, we're pretty unlikely to make a vaccine," Schief said.

The two other papers showed that although immune cells in mice can make a close cousin of the VRC01 antibody, it can only bind to a small number of HIV strains. The antibody would need to undergo many more mutations — brought on by further immunizations — within the cell before it can consistently bind to a large enough number of HIV strains.

This would likely require multiple immunizations, each causing the antibody to further mutate until its targets are sufficiently broad. While the first step is clear, the following steps are still unknown.

"We're closing in on some pieces that may eventually end up in a candidate vaccine," Schief said. "We just need to add some more pieces to the puzzle."

These attempts to turn the body into a factory for BNABs are still a long ways off from a vaccine that’s testable in people.

Instead of going the vaccine route, some researchers are trying to inject BNABs directly into humans — almost like a drug. But because people aren't producing the BNABs on their own, such an approach is viewed as an impractical way to solve such a large-scale problem.

"If you think about Africa, where we spend a lot of our time working," Koff said, "is it really a solution to infuse people with antibodies every eight weeks, for essentially a lifetime?"

Yet another approach inserts genes for the BNABs directly into muscle cells. While this has been shown to be effective for a lifetime in mice and for several years in monkeys, it remains to be seen whether it lasts long enough — and is safe — in people.

While some AIDS advocates have argued that finding a vaccine needs to be made more of a research priority, the fact is it's an incredibly difficult scientific problem — not a financial one.

"We're making vaccine research the highest priority of anything that we're doing," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told BuzzFeed News. "More money is going towards [the vaccine] than any other component of HIV research."

According to the National Institutes of Health Office of AIDS Research, NIH has spent approximately $500 million a year on finding an HIV vaccine for the last decade. In 2013, U.S. funding towards an AIDS vaccine made up more than 60% of the global total.

"We can't ignore the fact that we've still got a very long way to go," said Schief of Scripps. "But these studies are a shot of encouragement."

Azeen Ghorayshi is a science reporter for BuzzFeed News and is based in New York. Her PGP Fingerprint is 672A 7C08 9443 A95F 9D85 78FB 91EB 9C30 B197 5963.